The objectives of this project are to understand some of the mechanisms by which the motor neurons respond to injury whether it be due to trauma or to biological or industrial toxins. Our strategy has been to produce animal models of human disease which can be studied with the approaches of contemporary neurobiology. Our major effort has been directed to developing strategies to the study of disorders of motor neurons and peripheral nerves. We are particularly interested in the idea the abnormalities of axonal transport may be important in a number of neurological diseases including tetanus, regeneration after axotomy, the neuropathies associated with acrylamide and hexanedione, and the neurofibrillary axonal swellings observed in intoxication with Beta, Beta-iminodipropionitrile (IDPN) and in a hereditary spinal muscular atrophy in Brittany spaniels. High resolution autoradiography, immunocytochemistry, gel electrophoresis and gel fluoroautoradiography have been used to answer specific questions concerning the mechanisms underlying these neuropathologic processes.